Developmental decrease in rat small intestinal creatine uptake

Phosphocreatine is an energy buffer and transducer in the heart, the brain and the skeletal muscle. Recently, we have demonstrated the presence of the Na+/Cl−/creatine transporter at the apical membrane of the small intestinal epithelium. Herein the ontogeny and segmental distribution of rat intestinal creatine transport activity are investigated. [14C]-Creatine uptake was measured in the jejunum and ileum of 16 day gestation foetuses, newborn, suckling, weaning, 1-, 2-, 7- and 12-month-old (adult) rats. Creatine content in amniotic fluid, in rat and commercial milk and in rat chow, was measured by HPLC. NaCl-dependent creatine uptake was maximal in newborn rats and, in all the ages tested, higher in the ileum than in the jejunum. In the latter, NaCl-dependent creatine uptake was undetectable after weaning. Kinetic studies revealed that the jejunum and ileum have the same creatine uptake system, and that maturation decreases its V max but not the apparent K m. Maintenance of the pups on a commercial milk diet supplemented with creatine prevented the ileal periweaning decline in creatine uptake activity, but not that in the jejunum. In 1-month-old rats, supplementation with creatine increased ileal, but not jejunal, creatine uptake. The results demonstrate for the first time that: (i) creatine uptake along the length of the small intestine is mediated by the same transport system, (ii) the activity of this transport system changes in a specific manner with maturation and (iii) these changes appear to be genetically programmed and controlled by the intestinal creatine content.